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Ying Lv,1,* Kun Zou,2,* Shanshan Zhuang,3 Yang Zhou,1 Yaping Weng,3 Enna Mi,1 Minzhu Xie,1 Long Wang1 1Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang,People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 3Department of Hemodialysis Center, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Lv, Department of Nephrology, The First Affiliated Hospital of Ningbo University, 59 Liuting Street, Ningbo, Zhejiang, 315010, People’s Republic of China, Email lvying0721@hotmail.comBackground: Hemodialysis-related restless legs syndrome (HD-RLS) is a common sensorial and motor disorder. The diagnosis of this disease is based on clinical criteria, and it has recently been proposed to use physiological parameters of the nerves related to the duration of the F wave as a supplementary diagnostic modality. The aim of the study is to determine the value of these parameters in the diagnosis of HD-RLS by comparing the differences between patients with HD-RLS and hemodialysis patients without RLS (HD-nRLS).Methods: A total of 20 HD-RLS patients, 33 HD-nRLS patients, and 30 age-and gender-matched healthy controls (HCs) were included in the study. The motor nerve conduction of the median and ulnar nerves in the upper limbs, as well as the tibial and peroneal nerves in the bilateral lower limbs, and the sensory nerve conduction of the sural nerve bilaterally and the superficial peroneal nerve, along with the F waves of the ulnar nerves, median nerve, and bilateral tibial nerve, were assessed.Results: Both groups of HD patients had variable levels of axonal degeneration and demyelination, with the HD-RLS patients having more severe lower limb involvement. The HD-RLS patients showed an extension of the F-wave duration (FWD) of the bilateral tibial, median, and ulnar nerves, along with an increased ratio between FWD and compound muscle action potential duration (CMAPD).Conclusion: Peripheral neuropathy occurs in patients with HD-RLS, and the FWD/CMAPD ratio could potentially serve as an adjunctive diagnostic tool for HD-RLS.Keywords: Restless legs syndrome, F wave hemodialysis, peripheral neuropathy

Cheng-Jie Mao,1,* Hao Peng,2,* Sheng Zhuang,1,* Ying-Chun Zhang,3 Wei-Ye Xie,1 Jia-Hui Yan,1 Hui-Hui Liu,1 Jing Chen,1 Jun-Yi Liu,4 Jianan Zhang,5 Hai Jiang,5 Yonghong Zhang,2 Mingzhi Zhang,2 Chun-Feng Liu1,6 1Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 3Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 4Department of Neurology, The Fourth Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Chronic Disease, Taicang Center of Disease Prevention and Control, Suzhou, People’s Republic of China; 6Institute of Neuroscience, Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun-Feng Liu, Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China, Email liuchunfeng@suda.edu.cn Mingzhi Zhang, Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park, Suzhou, 215123, People’s Republic of China, Email zhangmingzhi@suda.edu.cnBackground: Sleep is critical in health problems including Parkinson’s disease (PD). This study examined the association between sleep characteristics and the likelihood of prodromal PD.Methods: At baseline examination of the Heart and Brain Investigation in Taicang (HABIT) study, potential PD biomarkers were obtained for 8777 participants aged over 50 years, and the probability of prodromal PD was assessed based on the Chinese expert consensus and Movement Disorder Society (MDS) criteria. General and component sleep characteristics were evaluated by the Pittsburgh Sleep Quality Index (PSQI). Median regression was applied to examine the association between sleep and the probability of prodromal PD, adjusting for age, sex, education level, physical activity, obesity, fast plasma glucose, lipids, and hypertension.Results: Based on China criteria, a higher level of PSQI score was significantly associated with a higher probability of prodromal PD (β = 0.02, 95% CI: 0.01– 0.03) and a higher risk of having an increased probability of prodromal PD (OR = 1.04, 95% CI: 1.02– 1.05). Compared to participants with good quality sleep, those with poor quality sleep had a 0.07% increased probability of prodromal PD (95% CI: 0.01– 0.13) and a 19% increased risk of having a high prodromal PD probability (95% CI: 1.04– 1.20). Similar associations between sleep quality and the probability of prodromal PD were also observed using the MDS criteria. Subjective sleep quality, sleep latency, habitual sleep efficiency, daytime dysfunction, and use of sleep medications were also associated with the probability of prodromal PD.Conclusion: Poor sleep quality was associated with a high probability of prodromal PD. Sleep may be helpful for understanding and intervention of prodromal PD.Keywords: prodromal Parkinson’s disease, sleep, Parkinson’s disease

Xianhui Zeng,1,&ast; Yuxi Yin,2,&ast; Tengfei Li,3 Shuilong Zhuang1 1Department of Critical Care Medicine, Yiyang Central Hospital of Hunan Province, Yiyang City, Hunan Province, 413099, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Yiyang Central Hospital of Hunan Province, Yiyang City, 413099, People’s Republic of China; 3Department of Emergency, Yiyang Central Hospital of Hunan Province, Yiyang City, 413099, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuilong Zhuang, Department of Critical Care Medicine, Yiyang Central Hospital of Hunan Province, 118 Kangfu North Road, Heshan District, Yiyang City, Hunan Province, 413099, People’s Republic of China, Email zhuangshuilong@21cn.comObjective: By evaluating the level of serum procalcitonin (PCT), thromboelastography (TEG) and platelet count (PLT) of patients with septic shock in intensive care unit (ICU), the predictive value of the combination of the three indicators on the short-term progression was discussed, which provided a new basis for early clinical diagnosis and disease evaluation.Methods: The clinical data of 130 patients with septic shock admitted to the IUC of our hospital from December 2021 to December 2023 were analyzed retrospectively. These subjects were divided into good prognosis group (n=78) and poor prognosis group (n=52) according to the 28 d deaths. The influencing factors were explored using the Multivariate logistic regression analysis. The value of single or combined PCT, PLT and TEG in predicting poor short-term prognosis was assessed using the receiver operating characteristic (ROC) curve.Results: The patients in poor prognosis group had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, serum PCT level, coagulation reaction time (R value) and coagulation formation time (K value), but lower PLT levels, final strength of coagulation (MA value) and coagulation formation rate (α angle) than those in good prognosis group (P< 0.001). PCT, R value and K value were risk factors (P< 0.001), while PLT, MA value and α angle were protective factors (P< 0.001). The area under the curve (AUC) of PCT, PLT and TEG predicting poor short-term progression was 0.813, 0.658 and 0.752, respectively. The AUC of combined three indicators was 0.905, which had the highest predictive value.Conclusion: Serum levels of PCT, PLT and TEG had certain value in predicting poor short-term progression of septic shock patients, and their combined diagnostic value was higher. Therefore, regular monitoring of these three indicators could provide certain guiding significance for the prevention and treatment of poor short-term prognosis in patients with septic shock.Keywords: calcitoninogen, thromboelastography, platelet count, infectious shock, Disease progression, predictive value

Sanmei Zhuang,1,&ast; Xiaohong Yu,1,&ast; Yupeng Zhang,1,&ast; Xiaoyang Chen2,&ast; 1Department of Respiratory and Critical Care Medicine, Jinjiang Municipal Hospital, Quanzhou, Fujian, 362200, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyang Chen, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, People’s Republic of China, Email 1073356693@qq.comBackground: EBV pneumonia with multiple cavitary pulmonary lesions is clinically rare. We analyzed the clinical characteristics, diagnosis and treatment, with an aim to enhance clinicians’ awareness of this disease and reduce misdiagnosis and missed diagnoses.Case Presentation: This paper presents A 59-year-old male patient’s initial symptoms included fever, cough, sputum, and asthma. The pulmonary CT imaging demonstrated multiple patchy and ground glass consolidation in both lungs, partial cavitary formation, and subpleural mesh lattice changes in the lower lobe of both lungs. Further analysis, including bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) and CT-guided percutaneous lung biopsy mNGS, supported the diagnosis of EBV pneumonia. The patient was treated with acyclovir antiviral therapy for a week, resulting in symptom relief. Follow-up lung CT scans indicated interval reduction of inflammatory lesions, cavities, and interstitial changes. As the patient’s condition improved significantly and he was discharged from hospital. The treatment was continued with oral acyclovir for 12 days. Subsequent outpatient follow-up CT performed 12 days after discharge revealed further improvement of the inflammatory lesions, as well as a reduction in cavitary and interstitial changes.Conclusion: The clinical imaging findings in the presented case were highly distinctive and have not been documented in either domestic or international literature. This uniqueness could have potentially contributed to misdiagnosis or overlooked diagnosis. mNGS of percutaneous lung puncture tissue is valuable for the diagnosis of infection with rare lung pathogens.Keywords: adult EBV pneumonia, metagenomic next-generation sequencing, imaging characteristics, diagnosis, treatment

Magnetostrictive materials transduce magnetic and mechanical energies and when combined with piezoelectric elements, evoke magnetoelectric transduction for high-sensitivity magnetic field sensors and energy-efficient beyond-CMOS technologies. The dearth of ductile, rare-earth-free materials with high magnetostrictive coefficients motivates the discovery of superior materials. Fe1-xGax alloys are amongst the highest performing rare-earth-free magnetostrictive materials; however, magnetostriction becomes sharply suppressed beyond x = 19% due to the formation of a parasitic ordered intermetallic phase. Here, we harness epitaxy to extend the stability of the BCC Fe1-xGax alloy to gallium compositions as high as x = 30% and in so doing dramatically boost the magnetostriction by as much as 10x relative to the bulk and 2x larger than canonical rare-earth based magnetostrictors. A Fe1-xGax - [Pb(Mg1/3Nb2/3)O3]0.7-[PbTiO3]0.3 (PMN-PT) composite magnetoelectric shows robust 90° electrical switching of magnetic anisotropy and a converse magnetoelectric coefficient of 2.0 × 10-5 s m-1. When optimally scaled, this high coefficient implies stable switching at ~80 aJ per bit.

Modern scattering-type scanning near-field optical microscopy (s-SNOM) has become an indispensable tool in material research. However, as the s-SNOM technique marches into the far-infrared (IR) and terahertz (THz) regimes, emerging experiments sometimes produce puzzling results. For example, "anomalies" in the near-field optical contrast have been widely reported. In this Letter, we systematically investigate a series of extreme subwavelength metallic nanostructures via s-SNOM near-field imaging in the GHz to THz frequency range. We find that the near-field material contrast is greatly impacted by the lateral size of the nanostructure, while the spatial resolution is practically independent of it. The contrast is also strongly affected by the connectivity of the metallic structures to a larger metallic "ground plane". The observed effect can be largely explained by a quasi-electrostatic analysis. We also compare the THz s-SNOM results to those of the mid-IR regime, where the size-dependence becomes significant only for smaller structures. Our results reveal that the quantitative analysis of the near-field optical material contrasts in the long-wavelength regime requires a careful assessment of the size and configuration of metallic (optically conductive) structures.

Xiaoxu Li,1,&ast; Shifang Zhuang,2,&ast; Lin He,2 Shanmei Wang,3 Ming Zhao,1 Xiaodong Lyu4 1Department of Neurosurgery, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China; 2Genskey Medical Technology Co., Ltd, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Lyu, Central Laboratory, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dongming Road, Zhengzhou, 450000, People’s Republic of China, Tel/Fax +8613523417973, Email zlyyxiaodonglyu1268@zzu.edu.cnAbstract: Nocardia brain abscess is relatively rare and generally occurs in immunodeficient patients. Here, we present the first case of brain abscess due to Nocardia brevicatena in an immunocompetent patient, with unknown origin. In this case, a 49-year-old man was admitted to our hospital with limb twitching and complained of a history of intermittent headache. He was diagnosed with brain abscess through brain imaging and cured after craniotomy for abscess excision and targeted antibiotic treatment. Surgical specimens were sent for further detection. The causative organism was identified by weak acid-fast staining, culture and metagenomic next-generation sequencing (mNGS). We hope this case could provide a reference for incoming patients as well as their clinical management.Keywords: brain abscess, Nocardia brevicatena, non-immunocompromised, mNGS, surgical treatment

Yi-Lun Ge,1,&ast; Si-Yi Gong,1,&ast; Pu-Zhi Wang,1 Jia-Hui Yan,1 Wen Li,1 Jin-Ru Zhang,1 Hong Jin,1 Sheng Zhuang,1 Lei Hu,2 Chang-Wei Ding,2 Ya-Ping Yang,1 Fen Wang,3 Dan Li,4 Jing Chen,1 Cheng-Jie Mao,1,4 Ying-Chun Zhang,2 Kai Li,1 Chun-Feng Liu1,3,4 1Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Ultrasound, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 4Department of Neurology, Suqian First Hospital, Suqian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Li, Department of Neurology, the Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, Jiangsu, 215004, People’s Republic of China, Tel +86-512-6778-4179, Fax +86-512-6828-4303, Email liskai@126.comPurpose: Cognitive impairment (CI) is a common but debilitating non-motor symptom in Parkinson’s disease (PD). Although cerebrovascular functions are related to cognitive performance in healthy individuals, such a relation in PD remains elusive. This study aims to assess the association between cerebrovascular function and cognitive performance in PD individuals.Patients and Methods: Two-hundred-and-one PD individuals were retrospectively included. They were subsequently divided into two groups: PD with normal cognition (PD-NC) and PD with CI (PD-CI). Cerebral hemodynamic characteristics of the middle cerebral arteries were assessed by transcranial ultrasound. The association between scores in each cognitive domain and cerebral hemodynamic parameters was further analyzed using regression analyses. Additionally, a binary logistic regression model with backward stepwise procedure was applied to build the model for discriminating CI in PD individuals. An independent dataset of additional 46 PD individuals was used further.Results: The PD-CI group showed a relatively lower end-diastolic blood flow velocity (EDV, p < 0.05) and a higher resistive index (RI, p < 0.05) compared to the PD-NC group. RI showed significant associations with the memory item score of Montreal Cognitive Assessment (p < 0.05). A model combining clinical and hemodynamic variables was established with optimal efficiency (area under the curve, AUC = 0.651). Further replication of the model in an independent dataset yielded a great consistency (AUC = 0.704).Conclusion: In our study, cerebrovascular functions were significantly associated with the cognitive performance in PD individuals, especially with the memory task. The established model was effective in identifying CI in PD individuals, which might be a potentially useful tool to screen the cognitive decline in PD individuals at an early stage of the disease. Further studies with larger sample sizes in different populations are warranted.Keywords: Parkinson’s disease, cognitive impairment, transcranial ultrasound, resistive index

Si-Yi Gong,1,&ast; Yun Shen,1,&ast; Han-Ying Gu,1 Sheng Zhuang,1 Xiang Fu,1,2 Qiao-Jun Wang,1 Cheng-Jie Mao,1 Hua Hu,1 Yong-Ping Dai,1 Chun-Feng Liu1– 3 1Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Neurology, Suqian First Hospital, Suqian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun-Feng Liu; Yong-Ping Dai, Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +86 512-67783307 ; +86 512-67784179, Fax +86 512-68284303, Email liuchunfeng@suda.edu.cn; dai_yongping@163.comPurpose: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is the prodromal marker of α-synuclein degeneration with markedly high predictive value. We aim to evaluate the value of electroencephalography (EEG) data during rapid eye movement (REM) sleep and subjective RBD severity in predicting the conversion to neurodegenerative diseases in iRBD patients.Methods: At the baseline, iRBD patients underwent clinical assessment and video-polysomnography (PSG). Relative spectral power for nine frequency bands during phasic and tonic REM sleep in three regions of interest, slow-to-fast ratios, clinical and PSG variables were estimated and compared between iRBD patients who converted to neurodegenerative diseases (iRBD-C) and iRBD patients who remained disease-free (iRBD-NC). Receiver operating characteristic (ROC) curves evaluated the predictive performance of slow-to-fast ratios, and subjective RBD severity as assessed with RBD Questionnaire-Hong Kong.Results: Twenty-two (33.8%) patients eventually developed neurodegenerative diseases. The iRBD-C group showed shorter total sleep time (p < 0.001), lower stage 2 sleep percentage (p = 0.044), more periodic leg-movement-related arousal index (p = 0.004), increased tonic chin electromyelographic activity (p = 0.040) and higher REM density in the third REM episode (p = 0.034) than the iRBD-NC group. EEG spectral power analyses revealed that iRBD phenoconverters showed significantly higher delta and lower alpha power, especially in central and occipital regions during the phasic REM state compared to the iRBD-NC group. Significantly higher slow-to-fast ratios were observed in a more generalized way during the phasic state in the iRBD-C group compared to the iRBD-NC group. ROC analyses of the slowing ratio in occipital areas during phasic REM sleep yielded an area under the curve of 0.749 (p = 0.001), while no significant predictive value of subjective RBD severity was observed.Conclusion: Our study shows that EEG slowing, especially in a more generalized manner during the phasic period, may be a promising marker in predicting phenoconversion in iRBD, rather than subjective RBD severity.Keywords: idiopathic rapid eye movement sleep behavior disorder, neurodegenerative diseases, EEG slowing, RBD severity, phenoconversion, neuroprotective therapy

The global steel sector is undergoing a transition from being a major CO2 emitter to a more sustainable circular material service provider, moving towards (near) net zero CO2 through combined strategies of reuse, remanufacturing, recycling and changes to primary steelmaking. This paper considers the transition using the UK as an example, based on the current sector state and future plans/opportunities. Some key enablers/barriers have been identified, and case studies are presented on the current state of knowledge and technology developments. For example, increasing reuse/remanufacturing requires data on the component's remaining life at the end-of-product life; in this work use of in-service monitoring for steel-intensive applications in the transport sector is discussed identifying sensor types/locations for fatigue loading assessment for different use conditions to feed into material/product passports for reuse/remanufacturing decisions. Increased recycling of obsolete scrap has implications for composition control with increases in residual elements, such as Cu, Sn, Cr and Ni inevitable. Current and future approaches to recycling and scrap sorting are discussed along with case studies for how residual elements affect microstructural development during steel processing, including effects on recrystallization, phase transformation and fine-scale precipitation, which potentially could be exploited to give increases in product strength. This article is part of the discussion meeting issue 'Sustainable metals: science and systems'. [ABSTRACT FROM AUTHOR]

Caigu He,1 Guang Liu,1 Shuting Zhuang,2 Jialin Zhang,2 Yangtao Chen,1 Hetian Li,1 Zhengping Huang,1 Yanfang Zheng3 1Department of Histology and Embryology, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, People’s Republic of China; 2Department of Biochemistry, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, People’s Republic of China; 3Department of Pharmacology, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, People’s Republic of ChinaCorrespondence: Caigu HeFujian University of Traditional Chinese Medicine, People’s Republic of ChinaEmail caiguheeel@163.comIntroduction: Yu Nu compound (YNJ) is a traditional Chinese medicine widely utilized to treat type 2 diabetes possibly through mediating autophagy. Abnormal podocyte autophagy and apoptosis could result in podocyte loss in diabetics nephropathy (DN). The mechanism of Yu Nu compound in DN is still unclear. Therefore, the study aims to investigate the effects of Yu Nu compound and analyze the potential mechanism.Methods: Goto-Kakizaki (GK) rats were administered using YNJ with different doses once a day by gavage for 4 weeks. The renal cortex injury was observed by HE staining and electron microscope. Cell apoptosis of renal cortex was analyzed by TUNNEL staining. The mTOR, autophagy-related proteins and apoptosis-related proteins were detected by Western blot or real-time PCR in vivo and vitro. MPC5 cells were exposed to high glucose (HG, 30mM) for 12h to simulate podocyte injury in DN. MPC5 cells were treated by serum containing YNJ with different dosages. Cell activities and apoptosis were, respectively, detected through Cell Counting Kit-8 (CCK8) assay and flow cytometry.Results: The results showed that the medium dose of YNJ had better effects on decreasing blood glucose and improving renal injury in GK rats, followed by decreasing mTOR levels. The autophagy levels were enhanced in renal cortex, accompanied with the increase of cell apoptosis in vivo. Besides, the proteins regulating autophagy and apoptosis were significantly modulated by YNJ in GK rats. Then, we found that the decreasing endogenous mTOR could reverse the effects of YNJ on podocyte apoptosis and autophagy in vivo.Discussion: The study suggested that YNJ recovered normal autophagy and suppressed apoptosis through regulating mTOR. The maintenance of normal basal autophagic activity possibly based on the effect of YNJ on multiple target was essential for maintaining podocyte function.Keywords: traditional Chinese medicine, diabetics nephropathy, LC3, Bcl-2, mTOR

Songwei Huan,1,* Tao Gui,1,* Qiutong Xu,1,* Songkuan Zhuang,2 Zhenyan Li,1 Yuling Shi,3 Jiebin Lin,3 Bin Gong,1 Guiqiang Miao,1 Manseng Tam,4 Huan-Tian Zhang,1 Zhengang Zha,1 Chunfei Wu3 1Institute of Orthopedic Diseases and Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong, People’s Republic of China; 2School of Life Science, Xiamen University, Xiamen, Fujian 361005, People’s Republic of China; 3Department of Orthopedics, The Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, People’s Republic of China; 4IAN WO Medical Center, Macao Special Administrative Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengang Zha; Chunfei Wu Tel +86-20-38688617; Tel +86-13610075186Fax +86-20-38688000; Email tbri@jnu.edu.cn; wuchunfei666@163.comBackground: Chondrosarcoma is the second-most common type of bone tumor and has inherent resistance to conventional chemotherapy. Present study aimed to explore the therapeutic effect and specific mechanism(s) of combination BET family protein and HDAC inhibition in chondrosarcoma.Methods: Two chondrosarcoma cells were treated with BET family protein inhibitor (JQ1) and histone deacetylase inhibitors (HDACIs) (vorinostat/SAHA or panobinostat/PANO) separately or in combination; then, the cell viability was determined by Cell Counting Kit-8 (CCK-8) assay, and the combination index (CI) was calculated by the Chou method; cell proliferation was evaluated by 5-ethynyl-2′-deoxyuridine (EdU) incorporation and colony formation assay; cell apoptosis and reactive oxygen species (ROS) level were determined by flow cytometry; protein expressions of caspase-3, Bcl-XL, Bcl-2, γ-H2AX, and RAD51 were examined by Immunoblotting; DNA damage was determined by comet assay; RAD51 and γ-H2AX foci were observed by immunofluorescence.Results: Combined treatment with JQ1 and SAHA or PANO synergistically suppressed the growth and colony formation ability of the chondrosarcoma cells. Combined BET and HDAC inhibition also significantly elevated the ROS level, followed by the activation of cleaved-caspase-3, and the downregulation of Bcl-2 and Bcl-XL. Mechanistically, combination treatment with JQ1 and SAHA caused numerous DNA double-strand breaks (DSBs), as evidenced by the comet assay. The increase in γ-H2AX expression and foci formation also consistently indicated the accumulation of DNA damage upon cotreatment with JQ1 and SAHA. Furthermore, RAD51, a key protein of homologous recombination (HR) DNA repair, was found to be profoundly suppressed. In contrast, ectopic expression of RAD51 partially rescued SW 1353 cell apoptosis by inhibiting the expression of cleaved-caspase-3.Conclusion: Taken together, our results disclose that BET and HDAC inhibition synergistically inhibit cell growth and induce cell apoptosis through a mechanism that involves the suppression of RAD51-related HR DNA repair in chondrosarcoma cells.Keywords: chondrosarcoma, JQ1, HDAC, apoptosis, RAD51, DNA repair

Xinhui Xie,1 Jialei Song,1 Yili Hu,1 Suyang Zhuang,1 Yuntao Wang,1 Yunlei Zhao,2 Qian Lu2 1Department of Orthopedics, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210093, China; 2Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu 210093, China Background: Development of the burgeoning number of photothermal therapy (PTT) agents has drawn a huge amount of interest, since PTT treatment is a powerful and effective alternative to traditional treatments. Optimal PTT agents should integrate some essential preconditions including negligible systemic toxicity, deep penetration into tumor tissues, and maximum laser energy absorbance. Unfortunately, only few of the PTT agents reported could meet all of the above mentioned conditions.Methods: Here, we report a brand new PTT agent through the encapsulation of NaGdF4:Yb,Tm@NaGdF4:Yb (UCNPs) and an organic compound (C3) into poly-e-caprolactone-polyethylene-polyglycol (PCL-PEG) (PL-UC-C3 NPs).Results: UCNPs as an up-conversion material and C3 as a PTT agent both feature low cytotoxicity, and most importantly, UCNPs with superior conversion efficiency could efficiently absorb the energy of a 980 nm laser, transform the near-infrared laser light into visible light, and translate the palingenetic visible light to C3. The usage of a 980 nm laser ensures a deeper penetration and lower energy, while the highly efficient absorption and transformation process confers a cascade amplified hyperthermia for tumor treatment.Conclusion: In this regard, our research provides a powerful and robust breakthrough for florescence/computed tomography imaging-guided PTT treatment, lighting up the clinical application in cancer treatment. Keywords: photothermal therapy, PCL-PEG, up-conversion, excellent photothermal stability, high heat conversion efficiency

Yue-Long Xu,1,* Xiu-Xiu Li,1,* Su-Jing Zhuang,1 Shi-Feng Guo,1 Jian-Ping Xiang,1 Long Wang,2 Lan Zhou,2 Bin Wu3 1Department of Neurology, Linyi Central Hospital, Linyi 276400, Shandong Province, China; 2Department of Neurology, Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China; 3Department of Stomatology, People’s Hospital of District Longhua Shenzhen, Shenzhen 518109, Guangdong Province, China *These authors contributed equally to this work Introduction: Previously published articles have suggested that BDNF rs6265 G>A polymorphism is a potential risk factor for epilepsy. However, the results were not consistent. Methods: We conducted a meta-analysis to explore the association between BDNF rs6265 G>A polymorphism and epilepsy risk. Four online databases were searched, and related studies were reviewed from their inception up to June 20, 2017. ORs and corresponding 95% CIs were used to calculate the associations of each genetic model. Overall, 10 case–control publications involving 9,512 subjects were included in this meta-analysis. Results: Significant associations were found between BDNF rs6265 G>A polymorphism and epilepsy (A vs G: OR=0.88, 95% CI=0.83–0.94, PA polymorphism might be involved in epilepsy susceptibility, especially in the Asian population. Keywords: brain derived neurotrophic factor, epilepsy, seizure, polymorphism, variant, rs6265, case–control

Wei Zhao, Song Zhuang, Xian-Rong QiDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of ChinaAbstract: Neutral liposomes (NLP) exhibit preferential localization in solid tumors based on the enhanced permeation and retention (EPR) effect. Cationic liposomes (CLP) have a propensity for localizing in newly formed tumor vessels and they have a potentially enhanced antitumor effect. However, an increased amount of cationic lipids in liposomes also induces aggregation through electrostatic interactions between the liposomes and the anionic species in the circulation, which results in a reduced EPR effect. Consequently, it is important to investigate the characteristics of liposomes with different surface potentials in vitro to achieve an optimal intratumoral distribution and antitumor effect in vivo. In this study, the authors evaluated the characteristics of doxorubicin (DOX)-loaded NLPs, CLPs, polyethylene glycol (PEG)-modified NLPs (NLP-PEG), and PEGylated CLPs (CLP-PEG) (ie, encapsulation efficacy, zeta potential, size, membrane fluidity, aggregation in serum, and uptake of liposomes into rat aortic endothelial cells (RAECs)) to further understand their influences on the pharmacokinetics, biodistribution, and antitumor therapy in vivo. The results showed that increased amounts of cationic lipids resulted in severe liposome aggregation in the presence of serum, yet it did not alter the membrane fluidity to a large extent. The uptake of liposomes into RAECs, visualized by confocal fluorescence microscopy, confirmed the rapid uptake of CLP by the endothelial cells compared with NLP. However, the pharmacokinetics, biodistribution and anticancer efficacies of these liposomes in vivo revealed that the CLP with highly positive surface potentials exhibited reduced circulation times and poor distribution in tumors. The NLP-PEG exhibited the highest anticancer efficacy; CLP-PEG, the second highest; and CLP with the most positive surface potential, the lowest. These phenomena were mostly due to the rapid aggregation in serum and subsequent accumulation in the lungs upon the intravenous injection of the CLP. Caution should be exercised when chemotherapeutic drugs are loaded into CLP for tumor therapy.Keywords: cationic liposomes, PEGylation, electrostatic interaction, aggregation, anticancer efficacy, biodistribution

1. This study investigated the effects of dietary betaine supplementation on growth performance, meat quality, muscle fatty acid composition and antioxidant ability in slow-growing broiler chickens. 2. In total, 400, one-day-old female Xueshan broiler chicks were randomly divided into five groups with eight replicates of ten chickens each for 102 d. Broilers were fed a basal diet supplemented with 0, 125, 250, 500 or 1,000 mg/kg betaine. 3. Broilers fed betaine had better feed conversion efficiency and weight gain (P < 0.05) and increased meat redness and yellowness 24 h after slaughter. Supplementation linearly decreased cooking loss and drip loss from breast muscle (P < 0.05). Muscular resilience was improved and tenderness increased (P < 0.05). Intra-muscular saturated fatty acids decreased, while total monounsaturated fatty acids and polyunsaturated fatty acids increased (P < 0.05). Betaine increased activities of glutathione peroxidase (GPx) and total superoxide dismutase (SOD), glutathione (GSH) level, ratio of reduced glutathione/oxidised glutathione, and activity of scavenging hydroxyl radicals. It increased the activity of total antioxidant capacity (T-AOC) in the breast muscle (P < 0.05). Moreover, supplementation up-regulated (P < 0.05) mRNA expression levels of blood and antioxidant markers. 4. In conclusion, 1000 mg/kg betaine can be recommended as a supplement for slow-growing, Xueshan chicken. [ABSTRACT FROM AUTHOR]

The present study was set out to explore the effects of diets supplemented with synbiotics, as a possible antibiotic substitute, on growth performance, intestinal barrier function and cecal microorganisms of Cherry Valley ducks. Briefly, a total of 540 Cherry Valley ducks (one-day-old) were randomly categorized into 3 groups for 42 days: control group (basal diets free from the antibiotic), antibiotic group (basal diets supplemented with 40 mg/kg bacitracin zinc), and synbiotic group (basal diets supplemented with 1 000 mg/kg synbiotic). Each group consisted of 6 replicates of 30 ducks each. In synbiotic group, average-day-gain (ADG) throughout the trial period (p=0.05) and average-day-feed-intake (ADFI) during the starter and grower periods (p=0.05) were increased as compared with the control group. Moreover, dietary synbiotics enhanced ileal villus height to crypt depth (V/C), decreased ileal crypt depth compared with the control group (p=0.05). In addition, the synbiotics increased numbers of Intraepithelial lymphocytes (IELs) and goblet cells in the small intestine (p=0.05), and secretory IgA (sIgA) concentration in the duodenum and jejunum (p=0.05) of 42-day-old ducks as compared with the control group. Furthermore, synbiotics supplementation increased the mRNA expression of jejunal mucosal occluding (OCLN) and the population of Bifidobacterium in cecal chyme (p=0.05). In conclusion, diets supplemented with synbiotics could improve growth performance and intestinal morphology, enhance intestinal barrier function, and modulate the cecal microorganisms in Cherry Valley ducks. [ABSTRACT FROM AUTHOR]